The DNA alphabet is not limited to the four standard nucleotides. Rather, twelve nucleobases forming six base pairs joined by mutually exclusive hydrogen bonding patterns are possible within the geometry of the Watson-Crick base pair. These form An Expanded Genetic Information System (Aegis), a new, "rule based" molecular recognition system that carries protein functionality, can be prepared in combinatorial form, and can be copied much like nucleic acids. Given the rich understanding of this system after a decade of research in the Benner laboratory, Aegis is a technology transfer opportunity. In the Phase I study, a comprehensive set of experiments validated the ability of Aegis to provide a set of orthogonal, non-cross reacting tags useful to support highly multiplexed (100 or more analytes) DNA diagnostics systems. These included studies in both solution and solid phase, with the Luminex instruments that support multiplexing, and with polymerases. In Phase II, we will prepare 1000 independently binding DNA-like tags, further develop tools to support genotyping of individual patients, and select for polymerases that incorporate both functionalized nucleotides and Aegis components into oligonucleotides. PROPOSED COMMERCIAL APPLICATION: Chemical systems that support "rule based molecular recognition" have wide commercial applicability, including in come "blue skies" (nanotechnology and molecular computing, for example). More immediately, the Aegis system here is supporting a commercial diagnostics system, and has led in the Phase I period to an assay that detects single nucleotide polymorphisms (SNPs). Such assays promise a revolution in predictive medicine and personalized care, with potential market value.